Since myosin is the source of force generation in muscle, an understanding of myosin function is essential to progress in the analysis and treatment of muscular defects. At present, however, the basic model of myosin function, the swinging cross-bridge model, remains unproven. Furthermore, while regions of the myosin molecule involved in ATP and actin binding have been identified, the roles of several highly conserved domains of the myosin molecule remain obscure. Cold-arrested myosin mutants represent tools for observing previously inaccessible aspects of myosin function, and most of the mutants to be studied lie in a region of unknown function. The mutants will be characterized in terms of 1) sequence changes leading to cold sensitivity, 2) ability to interact with actin during cold arrest, 3) point in the ATPase cycle at which they are blocked, and 4) morphology of cold-arrested actomyosin complexes. By determining the point in the ATPase cycle at which the mutants arrest, and the morphology of the actomyosin complexes at these points, the role of the highly conserved region can be determined and key postulates of the swinging cross-bridge model and be investigated.